Evaluation of DNA/DNA and prime-boost vaccination using LPG3 against Leishmania major infection in susceptible BALB/c mice and its antigenic properties in human leishmaniasis

One of the main issues in vaccine development is implementation of new adjuvants to improve the antigen presentation and eliciting the protective immune response. Heat shock protein (HSP) molecules are known as natural adjuvants. They can stimulate the innate and adaptive immune response against infectious diseases and cancer. Lipophosphoglycan 3 (LPG3), the Leishmania homologous with GRP94 (glucose regulated protein 94), a member of HSP90 family, is involved in assembly of LPG as the most abundant macromolecule on the surface of Leishmania promastigotes. In the present study as a primary step, we tested LPG3 as a vaccine candidate in two regimens, DNA/DNA and prime-boost (DNA/Protein), against Leishmania major infection in BALB/c mice model. Our results showed that LPG3 and its fragment (rNT-LPG3) are highly immunogenic in BALB/c mice and can stimulate the production of both IgG1 and IgG2a. In prime-boost immunization strategy, the level of antibody response was higher compared with DNA/DNA immunization. The levels of IFN-γ in the supernatant of splenocytes from mice immunized with DNA/DNA and prime-boost regimens were significantly higher when compared to control groups. In fact, immunization with prime-boost vaccination has higher ratio of IFN-γ/IL-5, suggesting a shift towards a Th1 response.In addition, sera reactivity against LPG3 in visceral leishmaniasis (VL) patients was significantly higher in comparison with cutaneous leishmaniasis (CL) patients. Therefore, we recommend further investigations on the usage of LPG3 co-delivery with candidate antigens for vaccine development against leishmaniasis.